Introduction
Thyroid hormones are produced in response of the thyroid gland to
thyroid stimulating hormone (TSH) secreted from anterior pituitary
gland. Circulating thyroid hormones in forms of T4 and T3 enter cells by
diffusion and, in some tissues, such as the thyroid and brain, by active
transport [1]. T3 is the active form of thyroid hormones which will
also be available to cells from local conversion of T4 into T3 in side
cells them self. This locally produced T3 can leave the cell and binds
to T3 receptors in other tissues. In humans, approximately 80 percent of
extrathyroidal T3 produced from T4 is produced
intracellularly [2,3]. Intracellular T3 binds to nuclear receptor
called Thyroid Receptor (TR). T3-TR complexes then bind to regulatory
regions contained in the genes that are responsive to thyroid hormone
and exerts its action [4].
There are two TRs, alpha (THRa) and beta (THRb) [4,5]. THRa is
mainly found in bones, intestine nervous system and heart while THRb is
found mainly in retina, ear, heart, nervous system and it’s the main
regulator of the negative feedback on pituitary thyroid axis [6].
Most patients diagnosed with RTH are found to have mutations in THRb
with variant mutations had been described. However, recently some
patients are found to have mutations in THRa [6]. Clinical
manifestation depends on the receptor affected and the magnitude of the
resistance. There is no specific treatment for RTH and multiple
modalities of treatment have been found in reviewing the literature.
In this article we are reporting case of RTH, confirmed with genetic
testing and found to have sequence variant mutation that is not well
described due to absence of genetic conclusive evidence.